Measurement of cardiac output and blood volume by non-invasive detection of indicator dilution

Abstract

A system for evaluating the cardiovascular system parameters using indicator dilution and non-invasive or minimally invasive detection methods is disclosed. Intravascular indicators are stimulated, and emission patterns detected for computation of cardiac output, cardiac index, blood volume and other indicators of cardiovascular health.

We claim:  
     
       1. A method of measuring at least one measurement of a physical parameter of the cardiovascular system of a subject comprising: 
       a. administering to the cardiovascular system of a subject a detectable amount of at least one indicator;  
       b. applying a first wavelength of light for exciting the indicator within the cardiovascular system and causing the indicator to emit a second wavelength of light;  
       c. detecting the magnitude of intensity of the second wavelength of light emitted from the indicator in the circulatory system using at least one photodetector proximately located to a detection area of the subject;  
       d. removing a blood sample containing indicator from the subject;  
       e. determining the concentration of the indicator in the removed blood sample; and  
       f. computing at least one physical parameter of the cardiovascular system of the subject using the determined concentration and the detected magnitude of intensity.  
     
     
       2. The method of  claim 1  wherein the second wavelength of light emitted from the indicator is caused by fluorescence of the indicator. 
     
     
       3. The method of  claim 1  wherein the measured parameter of the cardiovascular system is cardiac output and wherein the method further comprises detecting the magnitude of intensity of the second wavelength of light emitted from the indicator over a time period, forming a magnitude of intensity curve for the time period, and wherein the mathematical analysis of cardiac output comprises at least one of curve fitting to a model equation or numerical integration. 
     
     
       4. The method of  claim 3  further comprising calculating the cardiac index by expressing the cardiac output as a function of either the subject's weight or the subject's surface area. 
     
     
       5. The method of  claim 1  wherein the measured parameter of the cardiovascular system is circulating blood volume and wherein the method further comprises detecting the magnitude of intensity of the second wavelength of light emitted from the indicator over a time period, forming a magnitude of intensity curve for the time period, and wherein the computing of blood volume comprises back extrapolating a slow phase of the intensity curve to determine circulating blood volume. 
     
     
       6. The method of  claim 1 , wherein the photodetector is placed in at least one of a transdermal detection area, a subdermal detection area, a perivascular detection area or an endovascular detection area. 
     
     
       7. The method of  claim 1 , wherein the detecting is performed in either transmission mode or reflection mode. 
     
     
       8. The method of  claim 1 , wherein steps a-c and f are repeated at a time interval to determine if the cardiovascular value for the subject has changed. 
     
     
       9. The method of  claim 1 , further comprising treating the patient with a stimulus and wherein steps a-c and f are repeated at a time interval to determine if the cardiovascular value for the subject has changed after exposure to the stimulus. 
     
     
       10. The method of  claim 1  wherein the detection area is arterialized by application of heat or pharmacologically prior to detecting the second wavelength of light at the detection area. 
     
     
       11. The method of  claim 1  wherein the first wavelength of light is within the range of about 750 nm to about 1000 nm. 
     
     
       12. The method of  claim 1  wherein the indicator is a chromophore or fluorophore emitting the second wavelength of light in a range from about 400 nm to about 1000 nm. 
     
     
       13. The method of  claim 1  wherein the fluorophores are selected from the group comprising indocyanine green, fluorescein and rhodamine. 
     
     
       14. The method of  claim 1  wherein the detecting the magnitude of intensity of the second wavelength and the removing a blood sample are performed at approximately the same time. 
     
     
       15. A method of measuring at least one of a physical parameter of the cardiovascular system of a subject comprising: 
       a. administering to the cardiovascular system of a subject a detectable amount of at least one indicator;  
       b. applying a first wavelength of light for exciting the indicator within the cardiovascular system and causing the indicator to emit a second wavelength of light within the range of about 750 nm to about 1000 nm,  
       c. detecting the magnitude of intensity of the second wavelength of light emitted from the indicator in the circulatory system using at least one photodetector proximately located to a detection area of the subject;  
       d. removing a blood sample containing indicator from the subject;  
       e. determining the concentration of the indicator in the removed blood sample; and  
       f. computing at least one physical parameter of the cardiovascular system of the subject using the determined concentration and the detected magnitude of intensity.  
     
     
       16. The method of  claim 15  wherein the measured parameter of the cardiovascular system is cardiac output and wherein the method further comprises detecting the magnitude of intensity of the second wavelength of light emitted from the indicator over a time period, forming a magnitude of intensity curve for the time period, and wherein the mathematical analysis of cardiac output comprises at least one of curve fitting to a model equation or numerical integration. 
     
     
       17. The method of  claim 16  further comprising calculating the cardiac index by expressing the cardiac output as a function of either the subject's weight or the subject's surface area. 
     
     
       18. The method of  claim 15  wherein the measured parameter of the cardiovascular system is circulating blood volume and wherein the method further comprises detecting the magnitude of intensity of the second wavelength of light emitted from the indicator over a time period, forming a magnitude of intensity curve for the time period, and wherein the computing of blood volume comprises back extrapolating a slow phase of the intensity curve to determine circulating blood volume. 
     
     
       19. The method of  claim 15 , wherein the photodetector is placed in at least one of a transdermal detection area, a subdermal detection area, a perivascular detection area, or an endovascular detection area. 
     
     
       20. The method of  claim 15 , wherein the detecting is performed in either transmission mode or reflection mode. 
     
     
       21. The method of  claim 15 , wherein steps a-c and f are repeated at a selected interval to determine if the cardiovascular value for the subject has changed. 
     
     
       22. The method of  claim 15 , further comprising treating the patient with a stimulus and wherein steps a-c and f are repeated at a selected interval to determine if the cardiovascular value for the subject has changed after exposure to the stimulus. 
     
     
       23. The method of  claim 15  wherein the detection area is arterialized by application of heat or pharmacologically prior to detecting the second wavelength of light at the detection area. 
     
     
       24. A system for determining parameters of the cardiovascular system of a subject comprising: 
       a. an illumination source configured to be positioned proximately to at least one blood vessel of the cardiovascular system for providing a first wavelength of light for exciting an indicator within the cardiovascular system and causing the indicator to emit a second wavelength of light;  
       b. a photodetector configured to be positioned proximate to at least one blood vessel of the cardiovascular system of the subject for detecting the magnitude of intensity of the second wavelength of light emitted from the indicator in the circulatory system and for transmitting electronic signals proportionate to the detected magnitude of intensity of the second wavelength of light to a computing system;  
       c. the computing system configured to compute at least one measurement of a physical parameter of the cardiovascular system of the subject based on the detected intensity of the second wavelength and the information indicative of the concentration of indicator in the blood that was derived from an analysis of a sample of blood containing indicator that was removed from the patient.  
     
     
       25. The system of  claim 24  further comprising at least one fiber optic probe operably connected to the illumination source for guiding the first wavelength of light from the illumination source to the detection area. 
     
     
       26. The system of  claim 24  further comprising at least one fiber optic probe operably connected to the photodetector for guiding the second wavelength of light from the detection area to the photodetector. 
     
     
       27. The system of  claim 24  further comprising at least one lock-in amplifier operably connected to the illumination source for modulating the first wavelength of light at a selected frequency, and operably connected to the photodetector for filtering the detection of the second wavelength of light at the selected frequency. 
     
     
       28. The system of  claim 24  wherein the measured parameter of the cardiovascular system is cardiac output and wherein the method further comprises detecting the magnitude of intensity of the second wavelength of light emitted from the indicator over a time period, forming a magnitude of intensity curve for the time period, and wherein the computing of cardiac output comprises at least one of curve fitting to a model equation or numerical integration. 
     
     
       29. The method of  claim 28  further comprising calculating the cardiac index by expressing the cardiac output as a function of either the subject's weight or the subject's surface area. 
     
     
       30. The method of  claim 24  wherein the measured parameter of the cardiovascular system is circulating blood volume and wherein the method further comprises detecting the magnitude of intensity of the second wavelength of light emitted from the indicator over a time period, forming a magnitude of intensity curve for the time period, and wherein the mathematical analysis of blood volume comprises back extrapolating a slow phase of the intensity curve to determine circulating blood volume. 
     
     
       31. The system of  claim 24 , wherein the photodetector is configured for placement in at least one of a transdermal detection area, a subdermal detection area, a perivascular detection area or an endovascular detection area. 
     
     
       32. The system of  claim 24  wherein the first wavelength of light is in the range of about 750 nm to about 1000 nm. 
     
     
       33. The system of  claim 24  wherein the indicator is a chromophore or fluorophore capable of emitting the second wavelength of light in a range from about 400 nm to about 900 nm. 
     
     
       34. A method of measuring at least one physical parameter of the cardiovascular system of a subject comprising: 
       a. administering to the cardiovascular system of a subject a detectable amount of at least one indicator;  
       b. applying a first wavelength of light for exciting the indicator within the cardiovascular system and causing the indicator to emit a second wavelength of light;  
       c. detecting the magnitude of intensity of the second wavelength of light emitted from the indicator in the circulatory system using at least one photodetector proximately located to a detection area of the subject;  
       d. filtering the light emitted by the indicator to substantially isolate the second wavelength of light;  
       e. analyzing mathematically the detected magnitude of intensity of the second wavelength of light to compute at least one physical parameter of the cardiovascular system of the subject.  
     
     
       35. A method of measuring at least one physical parameter of the cardiovascular system of a subject comprising: 
       a. administering to the cardiovascular system of a subject a detectable amount of at least one indicator;  
       b. applying a first wavelength of light for exciting the indicator within the cardiovascular system and causing the indicator to emit a second wavelength of light within the range of about 750 nm to about 1000 nm,  
       c. detecting the magnitude of intensity of the second wavelength of light emitted from the indicator in the circulatory system using at least one photodetector proximately located to a detection area of the subject;  
       d. filtering the light emitted by the indicator to substantially isolate the second wavelength of light; and  
       e. analyzing mathematically the detected magnitude of intensity of the second wavelength of light to compute at least one physical parameter of the cardiovascular system of the subject.  
     
     
       36. A system for determining parameters of the cardiovascular system of a subject comprising: 
       a. an illumination source configured to be positioned proximately to at least one blood vessel of the cardiovascular system for providing a first wavelength of light for exciting an indicator within the cardiovascular system and causing the indicator to emit a second wavelength of light;  
       b. a photodetector configured to be positioned proximate to at least one blood vessel of the cardiovascular system of the subject for detecting the magnitude of intensity of the second wavelength of light emitted from the indicator in the circulatory system and for transmitting electronic signals proportionate to the detected magnitude of intensity of the second wavelength of light to a computing system; and  
       c. a filter configured to filter the light emitted by the indicator to substantially isolate the second wavelength of light; and  
       d. the computing system for receiving the electronic signals and analyzing mathematically the detected magnitude of intensity to compute at least one physical parameter of the cardiovascular system of the subject.